Structure-Based Design and Optimization of Methionine Adenosyltransferase 2A (MAT2A) Inhibitors with High Selectivity, Brain Penetration, and In Vivo Efficacy.

Synthetic lethality has recently emerged as a new approach for the treatment of mutated genes that were previously considered undruggable. Targeting methionine adenosyltransferase 2A (MAT2A) in cancers with deletion of the methylthioadenosine phosphorylase (MTAP) gene leads to synthetic lethality and thus has attracted significant interest in the field of precise anticancer drug development. Herein, we report the discovery of a series of novel MAT2A inhibitors featuring a pyrazolo[3,4-]quinolin-4-one skeleton based on structure-based drug design.

Bisacenaphthopyrazinoquinoxaline derivatives: synthesis, physical properties and applications as semiconductors for n-channel field effect transistors.

Several bisacenaphthopyrazinoquinoxaline (BAPQ) based derivatives 1-3 were synthesized by condensation between the acenaphthenequinones and 1,2,4,5-tetraaminobenzene tetrahydrochloride. Their optical, electrochemical and self-assembling properties are tuned by different substituents. Among them, compound 3 possesses a homogeneously distributed low-lying LUMO due to the peripheral substitution with four cyano groups.

Large-size linear and star-shaped dihydropyrazine fused pyrazinacenes.

Linear and star-shaped pyrazinacenes 1a-b and 2 were synthesized via condensation between a new building block 11 and pyrene tetraones or cyclohexaone. Compound 2 represents the largest star-shaped dihydropyrazine fused pyrazinacene reported so far. These largely expanded pyrazinacenes show good solubility and have a strong tendency to aggregate in both solution and thin films, indicating their potential applications for organic electronic devices.